Mutations in the lungs of gpt delta transgenic mice following inhalation of diesel exhaust

Akiko H. Hashimoto, Kimiko Amanuma, Kyoko Hiyoshi, Yoshiki Sugawara, S. Goto, Rie Yanagisawa, Hirohisa Takano, Ken Ichi Masumura, Takehiko Nohmi, Yasunobu Aoki

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Diesel exhaust (DE) is a major airborne pollutant of urban areas. It contains various polycyclic aromatic hydrocarbons (PAH) and nitrated PAHs. In this study, gpt delta mice were treated with inhalation of 1 or 3 mg m -3 DE, or a single intratracheal instillation of diesel exhaust particles (DEP) or DEP extract. In the lungs of mice treated with inhalation of 3 mg m-3 DE for 12 weeks, the mutant frequency (MF) was 3.2-fold higher than that of the control group (1.90 × 10-5 and 0.59 × 10-5, respectively). An instillation of DEP and DEP extract resulted in a significant dose-dependent linear increase in MF. In mice treated with 0.5 mg DEP and 0.2 mg DEP extract, the MFs were 3.0- and 2.7-fold higher than that of the control group, respectively. The mutagenic potency (MF mg -1) of DEP extract (5.6 × 10-5) was double that of DEP (2.7 × 10-5), suggesting that the mutagenicity of the latter is derived primarily from compounds in the extract, which itself is responsible for ca. 50% of the weight of DEP. G:C→A:T transitions were the predominant gpt mutation induced by all three treatments and G:C→T:A transversions were induced by DEP and DEP extract. Guanine bases centered in nucleotide sequences such as GGA, TGA, CGG, and CGT were the major mutation targets of all three treatments. Thus, our results suggest that the mutagens contained in DEP such as PAH and nitrated PAHs induce mutations and may be responsible for carcinogenesis caused by inhalation of DE.

Original languageEnglish
Pages (from-to)682-693
Number of pages12
JournalEnvironmental and Molecular Mutagenesis
Volume48
Issue number8
DOIs
Publication statusPublished - Oct 2007

Fingerprint

Vehicle Emissions
Inhalation
Transgenic Mice
diesel
mutation
Lung
Mutation
PAH
Polycyclic Aromatic Hydrocarbons
Polycyclic aromatic hydrocarbons
particle
fold
Control Groups
mutagenicity
Mutagens
Guanine

Keywords

  • 6-thioguanine selection
  • Diesel emission
  • Diesel exhaust particles

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Genetics
  • Genetics(clinical)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Hashimoto, A. H., Amanuma, K., Hiyoshi, K., Sugawara, Y., Goto, S., Yanagisawa, R., ... Aoki, Y. (2007). Mutations in the lungs of gpt delta transgenic mice following inhalation of diesel exhaust. Environmental and Molecular Mutagenesis, 48(8), 682-693. https://doi.org/10.1002/em.20335

Mutations in the lungs of gpt delta transgenic mice following inhalation of diesel exhaust. / Hashimoto, Akiko H.; Amanuma, Kimiko; Hiyoshi, Kyoko; Sugawara, Yoshiki; Goto, S.; Yanagisawa, Rie; Takano, Hirohisa; Masumura, Ken Ichi; Nohmi, Takehiko; Aoki, Yasunobu.

In: Environmental and Molecular Mutagenesis, Vol. 48, No. 8, 10.2007, p. 682-693.

Research output: Contribution to journalArticle

Hashimoto, AH, Amanuma, K, Hiyoshi, K, Sugawara, Y, Goto, S, Yanagisawa, R, Takano, H, Masumura, KI, Nohmi, T & Aoki, Y 2007, 'Mutations in the lungs of gpt delta transgenic mice following inhalation of diesel exhaust', Environmental and Molecular Mutagenesis, vol. 48, no. 8, pp. 682-693. https://doi.org/10.1002/em.20335
Hashimoto, Akiko H. ; Amanuma, Kimiko ; Hiyoshi, Kyoko ; Sugawara, Yoshiki ; Goto, S. ; Yanagisawa, Rie ; Takano, Hirohisa ; Masumura, Ken Ichi ; Nohmi, Takehiko ; Aoki, Yasunobu. / Mutations in the lungs of gpt delta transgenic mice following inhalation of diesel exhaust. In: Environmental and Molecular Mutagenesis. 2007 ; Vol. 48, No. 8. pp. 682-693.
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